Delta-piperidinobutyl diphenylacetate salt of penicillin



Patented Oct. 6, 1953 2,654,743

UNITED STATES PATENT OFFICE DELTA-PIPERIDINOBUTYL DIPHENYLACE- TATE SALTOF PENICILLIN Harley W. Rhodehamel, Jr., Indianapolis, Ind., assignor toEli Lilly and Company, Indianapolis, Ind., a corporation of Indiana NoDrawing. Application February 13, 1952, Serial No. 271,433

2 Claims. (Cl. 260239.1)

This invention relates to a novel penicillin salt upon the slightlysoluble A-piperidinobutyl diand the preparation thereof. phenylacetatesalt of penicillin G precipitates.

I have discovered that A-piperidinobutyl di- The salt is separated, anddried in vacuo. phenylacetate or its salts can be combined withA-piperidinobutyl diphenylacetate can be prepenicillin or its salts byneutralization or meta- 5 pared by esterification of diphenylacetic acidwith thetical reactions to form a sparingly soluble A-piperidinobutanolaccording to the usual penicillin salt, thereby afiording a means of'pre methods. Acid addition salts of A-piperidinocipitating penicillinfrom solution, and of purifybutyl diphenylacetate thus prepared areformed ing penicillin. Moreover, the novel penicillin salt by ordinaryprocedures, such as, for example, can be utilized therapeutically, Aprolonged interreaction of equivalent amounts of the base penicillinblood level can be secured upon adand an acid in inert solvent solution,followed by ministering the salt parenterally by methods removal of thesolvent. known to the medical art. I claim:

Th foll win x mple illustrate the pr p ra- 1. The A-piperidinobutyldiphenylacetate salt tion of the novel salt of this invention: ofpenicillin represented by the following formula in which P representspenicillin: Example 1 To 3 g. of a solution of penicillin (e. g. a com-E mercial mixture of the several penicillins) disono-o-cmcmcmcm-or omsolved in 50 ml. of amyl acetate are added 3 g. of 3 A-piperidinobutyldiphenylacetate dissolved in ml. of amyl acetate. The mixture is cooledand 2 The A pjperidinobuty1 djphenylacetate t stirred occasionallywhereupon the A-pipericlinoof p nicillin, butyl diphenylacetate salt ofpenicillin precipi- HARLEY RHODEHAMELI JR tates. The salt is isolated asby decantation or 25 filtration, and dried in vacuo.

The salt is represented by the following for- References clted m the meof thls patent mula in which P represents penicillin: UNITED STATESPATENTS Number Name Date CH CH T- 2 2,515,898 Rhodehamel July 18,1950

CHC-0CHzCH2CHaOHz-N\ /CH2 P TE TS 3 P OHPCH, FOREIGN A N Number CountryDate Example 2 659,775 Great Britain Oct. 24, 1951 To an aqueoussolution of 0.3 g. of the potassi- F F REFER EN?Es um salt of penicillinG in 1.8 ml. of water is added Ballaro: Ciencia e Investigacion, vol. 4,Noa solution of 0.3 g. of A-piperidinobutyl diphenylvember 1948, pp.481, 482. acetate hydrochloride in 25 ml. of water. The Rhodehamel: "J.Am. Chem. Soc, vol. 73,

mixture is cooled and stirred occasionally where- 40 December 1951, p.5902.

1. THE $-PIPERIDINOBUTYL DIPHENYLACETATE SALT OF PENICILLIN REPRESENTEDBY THE FOLLOWING FORMULA IN WHICH P REPRESENTS PENICILLIN: